Psychiatric comorbidity: a concept in need of a theory.

Despite being a relatively new concept, psychiatric comorbidity, i.e. the co-occurrence of two or more mental disorders, has become widespread in clinical practice and psychiatric research. In this article, we trace the origin of the concept of psychiatric comorbidity, discuss the conceptual literature and point to basic problems concerning inadequate definition of the concept, differential diagnostic issues, and reification of mental disorders. We illustrate how these problems may have consequences for diagnostic assessment in current clinical practice and psychiatric research. To address some of the problems related to psychiatric comorbidity, we discuss potential principles for assessing psychiatric comorbidity. Inspired by Feinstein's original concept of comorbidity in general medicine and his differential diagnostic principles, we emphasize the importance of independence of mental disorders when assessing psychiatric comorbidity. We suggest that knowledge of trait v. state conditions and of the multitudinous clinical manifestations beyond what is captured in the diagnostic manuals may be helpful for assessing the independence of mental disorders and thus psychiatric comorbidity. We further argue that a more hierarchical diagnostic system and explicit exclusionary rules could improve clinical practice and research by reducing informational complexity and combating unwarranted psychiatric comorbidity.

Disordered Selfhood in Schizophrenia and the Examination of Anomalous Self-Experience: Accumulated Evidence and Experience.

Disordered selfhood in schizophrenia was rediscovered at the turn of the millennium. In 2005, Psychopathology published the psychometric instrument, the Examination of Anomalous Self-Experience (EASE). In this article, we summarize the historical background of the creation of the EASE, explicate the notion of the disorder of basic or minimal self with the help of phenomenological philosophy, and provide a brief description of clinical manifestations targeted by the EASE. We also present our personal experience using and teaching the EASE and summarize the empirical evidence obtained so far. We conclude that the basic self-disorder represents a crucial phenotype of schizophrenia spectrum disorders and that this phenotype offers a potential avenue to empirical pathogenetic research and psychotherapeutic treatment.

Schizophrenia-spectrum psychopathology in obsessive-compulsive disorder: an empirical study.

The differential diagnosis of obsessive-compulsive disorder (OCD) and schizophrenia-spectrum disorders can be difficult. In the current diagnostic criteria, basic concepts such as obsession and delusion overlap. This study examined lifetime schizophrenia-spectrum psychopathology, including subtle schizotypal symptomatology and subjective anomalies such as self-disorders, in a sample diagnosed with OCD in a specialized setting. The study also examined the differential diagnostic potential of the classic psychopathological notions of true obsession ('with resistance') and pseudo-obsession. The study involved 42 outpatients diagnosed with OCD at two clinics specialized in the treatment of OCD. The patients underwent semi-structured, narrative interviews assessing a comprehensive battery of psychopathological instruments. The final lifetime research-diagnosis was based on a consensus between a senior clinical psychiatrist and an experienced research clinician. The study found that 29% of the patients fulfilled criteria of schizophrenia or another non-affective psychosis as main, lifetime DSM-5 research-diagnosis. Another 33% received a research-diagnosis of schizotypal personality disorder, 10% a research-diagnosis of major depression and 29% a main research-diagnosis of OCD. Self-disorders aggregated in the schizophrenia-spectrum groups. True obsessions had a specificity of 93% and a sensitivity of 58% for a main diagnosis of OCD. In conclusion, a high proportion of clinically diagnosed OCD patients fulfilled diagnostic criteria of a schizophrenia-spectrum disorder. The conspicuous obsessive-compulsive symptomatology may have resulted in a disregard of psychotic symptoms and other psychopathology. Furthermore, the differentiation of obsessions from related psychopathological phenomena is insufficient and a conceptual and empirical effort in this domain is required in the future.

EAFI: Examination of Anomalous Fantasy and Imagination.

The Examination of Anomalous Fantasy and Imagination (EAFI) is an instrument for a semistructured, phenomenological exploration of psychopathology of imagination. The EAFI provides a conceptual-descriptive framework to address such experiences. It consists of 16 main items, sometimes divided into subtypes. We suggest that the anomalies of imagination explored by the EAFI reflect an alteration in the structure of consciousness and belong to a fundamental, generative layer of psychopathology with relevance to differential diagnostic purposes.

A Phenomenological Approach to Psychopathology of Imagination: Development of a Descriptive Instrument - Examination of Anomalous Fantasy and Imagination.

This paper serves as an introduction to the Examination of Anomalous Fantasy and Imagination (EAFI) - a novel instrument for a semistructured, phenomenological exploration of psychopathology of imagination. We present an account of the phenomenology of imagination and proceed to a presentation of the disorders of imagination that are addressed in the EAFI. Furthermore, the interrater reliability of the EAFI was examined in a diagnostically heterogeneous sample of 20 in-patients. The interrater agreement ranged from 0.6 to 1.0, with an average κ of 0.84. The internal consistency of the EAFI as measured by Cronbach's α was above 0.88. We suggest that the anomalies of imagination explored by the EAFI reflect an alteration of the structure of consciousness and belong to a fundamental, generative layer of psychopathology. These disorders may have relevance for differential diagnostic purposes, especially in first-contact, young patients.

Anomalies of Imagination and Disordered Self in Schizophrenia Spectrum Disorders.

Vivid mental imagery occurs frequently in schizophrenia spectrum disorders (SSDs). Overlapping phenomena, such as obsessions or ruminations, are also frequent in other psychiatric disorders, raising significant diagnostic challenges. Unfortunately, contemporary operational psychopathology lacks the epistemological and phenomenological framework to address such questions. Using the resources of phenomenology and philosophy of mind, we articulate the structure of imagination and describe its distinctive modifications in the SSDs. Drawing on pilot data with patients' self-descriptions, we present the notion of perceptualized imagery. The anomalous imagery acquires spatialization, spatiotemporal constancy, explorability, autonomy and a sense of experiential distance between the subject and the image. As a quasi-perceptual, stable object, such imagery often evokes an intense affective response, whereas the normal sense of 'irreality' of the fantasy may become compromised. We articulate these anomalies of imagination as being entailed by the underlying generative disorder of schizophrenia, namely the disorder of minimal self (unstable ipseity or first-person perspective). We propose that pathology of imagination is an important psychopathological aspect of the schizophrenia spectrum, with significant relevance for early diagnosis and differential diagnosis.

Anomalies of imagination and development of psychosis: A phenomenological account.

In 20th century psychiatry, various disturbances of imagination were discussed in the context of schizophrenia. Today, these notions have almost completely vanished from mainstream psychopathology. However, recent work has suggested that specific phenomena within this area have a relevance for differential diagnosis and early detection of psychosis. This paper first provides an overview of 20th century psychopathological literature, as well as more recent neurocognitive studies, addressing disturbances of imagination and their role for symptom formation in schizophrenia. It then discusses recent empirical investigations of subjective anomalies of imagination in schizophrenia-spectrum disorders and suggests a clinical-phenomenological account of their role in the development of psychotic symptoms. Empirically and conceptually, these subjective anomalies are linked with disturbances of basic self. Patients' descriptions of the development of their anomalous experiences and symptoms indicate that increased spatial (object-like) articulation and instability of the first-personal manifestation of imaginative experience can be involved in the emergence of delusions and hallucinatory phenomena. Finally, a potential link between subjective anomalies of imagination and the neurocognitive construct of source monitoring deficits is discussed.

Obsessive-compulsive symptoms in the schizophrenia-spectrum: current developments in psychopathology research.

PURPOSE OF REVIEW: Schizophrenia-spectrum disorders (SSD) frequently involve symptoms that usually are ascribed to nonpsychotic disorder spectra, such as obsessive-compulsive symptoms (OCS). These symptoms can cause differential diagnostic challenges, particularly in early illness stages, and must be considered in treatment planning. In this review, we provide an overview of recent literature within the field of OCS in SSD, with a focus on psychopathology research. RECENT FINDINGS: OCS are seen in approximately a quarter of patients with SSD or at-risk mental state of psychosis. They are associated with more severe clinical features and specific temporal patterns of OCS may be linked with different clinical trajectories. However, the current definitions of OCS have been criticized for their overinclusive nature, which is a limiting step for differential diagnosis and more precise prognostic stratification. Specific phenomenological features, including a link with experiential anomalies (disorders of basic self), have been suggested to provide clinically relevant distinctions. SUMMARY: The presence of OCS in SSD is associated with more severe clinical features and invites a higher clinical attention and perspectival monitoring. Some findings suggest that more fine-grained psychopathological distinctions might be a viable clinical and research strategy to advance the field in the direction of precision psychiatry.

Are Self-disorders in Schizophrenia Expressive of a Unifying Disturbance of Subjectivity: A Factor Analytic Approach.

BACKGROUND AND HYPOTHESIS: The idea that a disorder of the basic self is a central feature in schizophrenia has recently been corroborated in a meta-analysis and a systematic review. Manifestations of the self-disorder can be systematically explored with the Examination of Anomalous Self-Experience (EASE). In this study, we examined the factorial structure of EASE, and diagnostic efficacy of EASE. We hypothesized that EASE will have a monofactorial structure as an instability of the basic self will result in multiple deformations of self-experience which would be meaningfully interrelated as aspects of a unifying Gestalt. DESIGN: EASE data for 226 patients suffering from various mental disorders were analyzed under a confirmatory factor analysis framework (CFA). Area under the receiver operating characteristic curve (AUC) was calculated for the total EASE sums, and sensitivity and specificity values for prediction of schizophrenia spectrum disorders based on different cut-offs were obtained. RESULTS: Fit indices for the CFA model: RMSEA = 0.036, SRMR = 0.100, CFI = 0.983, TLI = 0.981. The AUC value was 0.946 (95% confidence interval: 0.919-0.974). Sensitivity as well as specificity for schizophrenia spectrum disorders were high. CONCLUSION: Our results lend support for EASE exhibiting a monofactorial structure and the notion of self-disorders as a central phenotypic feature of schizophrenia spectrum disorders.

Treatment of schizotypal disorder: a protocol for a systematic review of the evidence and recommendations for clinical practice.

INTRODUCTION: Schizotypal disorder is associated with a high level of disability at an individual level and high societal costs. However, clinical recommendations for the treatment of schizotypal disorder are scarce and based on limited evidence. This review aims to synthesise the current evidence on treatment for schizotypal disorder making recommendations for clinical practice. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search will be performed in PsychArticles, Embase, Medline and Cochrane Central Register of Controlled Trials. Additionally, we will search for relevant articles manually. Inclusion criteria are published studies including individuals diagnosed with schizotypal personality disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, or schizotypal disorder according to International Classification of Diseases (ICD) criteria. We will include interventional studies comprising any pharmacological and non-pharmacological treatment trials for patients with schizotypal disorder, and all relevant outcome measures will be reported. Risk of bias will be assessed by Cochrane risk-of-bias tools. Data will be synthesised using narrative or thematic analysis and, if suitable, through meta-analysis. ETHICS AND DISSEMINATION: No original data will be collected as part of this study and ethics approval is, therefore, not applicable. The results will be disseminated through peer-reviewed publication and presented at international scientific meetings. We will aim at submitting the final paper for publication within 4 months of completion of analyses. Furthermore, this systematic review will inform clinicians and researchers on the current state of evidence on treatment for schizotypal disorder. Findings may guide proposals for further research and potentially guide recommendations for clinical practice using the Grading of Recommendations Assessment, Development and Evaluation. PROSPERO REGISTRATION NUMBER: CRD42022375001.

What is obsession? Differentiating obsessive-compulsive disorder and the schizophrenia spectrum.

Obsessive-compulsive symptoms are frequent in schizophrenia-spectrum disorders and often cause differential diagnostic challenges, especially in first-contact patients. Drawing upon phenomenology of cognition, we critically review classic and contemporary psychopathological notions of obsessive-compulsive phenomena and discuss their relevance for differential diagnosis between obsessive-compulsive disorder (OCD) and schizophrenia-spectrum disorders. The classic psychopathological literature defines true obsession as intrusions with intact resistance and insight and regards these features as essential to the diagnosis of OCD. In schizophrenia, the classic literature describes pseudo-obsessive-compulsive phenomena characterized by lack of resistance and an affinity with other symptoms such as thought disorder and catatonia. By contrast, the notions of obsession and compulsion are broader and conceptually vague in current diagnostic systems and research instruments. Here, these phenomena overlap with delusions as well as various subjective and behavioral anomalies, which we discuss in detail. Furthermore, we examine a link between obsessive-compulsive phenomena and disturbances of basic structures of experience in schizophrenia-spectrum disorders addressed in contemporary psychopathological research. We suggest that these experiential alterations have relevance for differential diagnosis and early detection in this complex symptom domain.

Pseudoneurotic symptoms in the schizophrenia spectrum: An empirical study.

BACKGROUND: Nonpsychotic symptoms (depression, anxiety, obsessions etc.) are frequent in schizophrenia-spectrum disorders. Twentieth century foundational psychopathological literature claimed that certain nonpsychotic symptoms (here termed pseudoneurotic symptoms) are relatively closely linked with the schizophrenia-spectrum, despite descriptive overlap with symptoms of other diagnoses. In this study, we investigated the association of pseudoneurotic and other nonpsychotic symptoms with the schizophrenia-spectrum as well as a hypothesis about an association of pseudoneurotic symptoms with disorder of basic self. METHODS: The sample (N = 226) comprised patients with non-affective psychosis (N = 119), schizotypal personality disorder (N = 51) and other mental illness (N = 56), who were examined with a comprehensive assessment of lifetime psychopathology. Informed by the literature, we constructed scales targeting pseudoneurotic symptoms and other, more general, nonpsychotic symptoms. RESULTS: Pseudoneurotic symptoms aggregated significantly in schizophrenia-spectrum disorders with an Area under the receiver operating characteristic curve of 0.84 (SE 0.03) for classifying patients with schizophrenia-spectrum disorders versus other mental illness. Patients with non-affective psychosis scored slightly, but significantly, higher on the scale targeting general nonpsychotic symptomatology than the other groups. In multiple regression analysis, pseudoneurotic symptoms were predicted by general nonpsychotic symptoms, disorders of basic self, and negative symptoms but not positive symptoms. CONCLUSION: The study supports that certain neurotic-like symptoms with specific descriptive features (pseudoneurotic symptoms) are associated with schizophrenia-spectrum disorders. It suggests that pseudoneurotic symptoms are linked with temporally stable schizophrenia psychopathology (disorder of basic self and negative symptoms).

Anomalies of Imagination, Self-Disorders, and Schizophrenia Spectrum Psychopathology: A Network Analysis.

BACKGROUND: Anomalies of imagination encompass disturbances of the basic experiential structure of fantasies and imagery that can be explored in a semi-structured way with the Examination of Anomalous Fantasy and Imagination (EAFI). We aimed (1) to examine the distribution of anomalies of imagination among different diagnostic groups and a group of healthy controls, and (2) to examine their relation with disorders of basic self, perceptual disturbances and canonical state psychopathology of the schizophrenia-spectrum (positive, negative and general symptoms). METHODS: The 81 participants included patients with schizophrenia or other non-affective psychosis (N = 32), schizotypal personality disorder (N = 15) or other mental illness (N = 16) and healthy controls (N = 18). The assessment encompassed EAFI, Examination of Anomalous Self-Experience (EASE), parts of Bonn Scale for the Assessment of Basic Symptoms (BSABS) and Positive and Negative Syndrome Scale (PANSS). For network analysis, the associations of EAFI with the other psychopathological variables were tested by Pearson's correlation coefficient and graphically represented using multidimensional clustering. Comparisons between correlations in the network were tested with Steiger's test. RESULTS: Anomalies of imagination aggregated significantly in schizophrenia-spectrum disorders compared to other mental illness and healthy controls with no difference between schizophrenia and schizotypal disorder. In the network analysis, anomalies of imagination were closely inter-connected with self-disorders. Although, the anomalies of imagination correlated moderately with perceptual disturbance and positive, negative and general state symptomatology, these dimensions aggregated separately and relatively distant in the network. CONCLUSIONS: The results support that anomalies of imagination are highly characteristic of schizophrenia-spectrum disorders and closely related to self-disorders.

The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin.

PURPOSE: Erlotinib, an epidermal-growth-factor receptor inhibitor, belongs to a new generation of targeted cancer therapeutics. Gastrointestinal side-effects are common and have been markedly aggravated when erlotinib is combined with cytostatics. We examined the effects of erlotinib alone and combined with the cytostatic, cisplatin, on the gastrointestinal tract and examined whether glucagon-like peptide-2 (GLP-2), an intestinal hormone with potent intestinotrophic properties, might counteract the possible damaging effects of the treatments. EXPERIMENTAL DESIGN: Groups of ten mice were treated for 10 days with increasing doses of erlotinib alone or in combination with cisplatin and/or GLP-2. Weight and length of the gastrointestinal organs were determined and histological sections were analyzed with morphometric methods as well as BrdU- and ApopTag-staining to determine mitotic and apoptotic activity. RESULTS: Erlotinib was found to induce small-intestinal and colonic growth inhibition through an increased apoptotic activity but had no effect on mitotic activity. The combined treatment with cisplatin synergistically aggravated the intestinal growth inhibition. Erlotinib, and especially the combination therapy, increased the weight of the stomach contents considerably. Concomitant treatment with GLP-2 counteracted the intestinal mucosal atrophy induced both by erlotinib alone and combined with cisplatin through a reduction of the apoptotic activity. There was no influence on the mitotic activity. CONCLUSIONS: The findings demonstrate that the intestinal mucosal damage induced by erlotinib alone and in combination with cisplatin can be counteracted by GLP-2 treatment, which might suggest a role for GLP-2 in the treatment of the gastrointestinal side-effects caused by these cancer therapeutics.